We investigated the synthesis of IGF-I binding proteins in vitro by normal mouse mesangial cells. The supernatant from mesangial cells contained a single species of binding protein, with a molecular weight of 30 kD. This protein, known as BP2, was not glycosylated. It was found to be released in higher amounts in cells at lower density than in confluent cells. It was also found that the cells expressed mRNA for this binding protein. The binding protein release was coordinately regulated with the production of IGF-I by the cells. Thus, IGFBP2 could participate in the control of mesangial proliferation. In addition, diseases associated with an increase in glomerular cell turnover could be partly due to a dysregulation in IGFBP production and release.